Dr. Sadegh Babashah received his Ph.D. in Molecular Genetics from Tarbiat Modares University, Tehran, Iran in 2011. He is currently working as an Assistant Professor in this university. Dr. Babashah received outstanding research awards such as the 15th Khwarizmi International Youth Award, December 2013 for excellence in the field of biotechnology and medicine. He has authored several original/review articles in peer-reviewed prestigious journals and also contributed to writing many scientific books as an editor/ contributing author.
The concept of cancer stem cells (CSCs) has great clinical implications because small subpopulations of CSCs have been identified in many different tumors (or leukemias) that are associated with poor clinical outcome. Mounting evidence supports central functions of leukemic stem cells (LSCs) in leukemogenesis, due to its distinct high potentials of self-renewal, pluripotent differentiation and apoptosis-resistance, contributing to therapeutic resistance and cancer progression. Self-renewal is discriminated from other proliferating processes since at least one of progeny is identical to the primary stem cell. Dysregulation of stem cell self-renewal is a likely requisite for the initiation, progression, and therapeutic resistance of cancer. A number of studies showed that quiescent chronic myeloid leukemia (CML) stem cells are relatively resistant to therapies that target rapidly dividing CML cells, and thus contribute to avoiding apoptosis, renew themselves, and survive long term. Therefore, inhibiting/eliminating CML stem cells will provide a new effective therapeutic approach for the treatment of leukemias. However, the mechanistic roles of CML stem cells in leukemogenesis are not well understood. The discovery of microRNAs (miRNAs), a large family of small non-coding RNA molecules, has provided a newer perspective on cancer research. Emerging evidence suggests that miRNAs participate in the regulation of tumor cell growth, migration, invasion, angiogenesis, metastasis, and drug resistance. Apart from the oncogenic and tumor suppressive roles of miRNAs as key regulators of gene expression in tumorigenesis, these small RNAs have been also recognized as potential modulators of CML stem cell characteristics mediated through the regulation of multiple pro-oncogenic signaling pathways. Our recent studies showed that abnormal expression of certain miRNAs is involved in dysregulation of essential stem cell maintenance pathways such as Hedgehog pathway, resulting in unlimited self-renewal and cancer progression. In this regard, our observations suggest a model in which miRNA functions may be required to efficiently impair the oncogenic potential of stem cell maintenance pathways. Taken together, it seems that targeting CML stem cell signature genes along with relevant miRNAs will provide a novel and more effective therapeutic approach for the eradication of CML stem cells, which will lead to the inhibition of CML recurrence.
Keywords: CML stem cells, self-renewal, oncogenic pathways, microRNA